Condition category
Mental and Behavioural Disorders
Date applied
03/08/2009
Date assigned
23/09/2009
Last edited
04/03/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
A stroke occurs when the blood supply to part of the brain is cut off, either due to a blood clot (an ischaemic stroke) or a blood vessel bursting (a haemorrhagic stroke). Stroke can lead to cognitive decline and dementia. Intensive lowering of blood pressure and/or lipids (LDL-cholesterol) may reduce the risk of dementia after stroke. The aim of this study is to find out whether intensive blood pressure and/or lipid lowering are better than moderate blood pressure and/or lipid lowering to prevent cognitive decline after stroke.

Who can participate?
Patients who have had an ischaemic or haemorrhagic stroke in the last three to seven months.

What does the study involve?
Participants with ischaemic stroke are randomly allocated to either moderate or intensive blood pressure lowering treatment and to either moderate or intensive lipid lowering treatment. Participants with haemorrhagic stroke are randomly allocated to either moderate or intensive blood pressure lowering treatment. The study is testing treatment strategies, not individual drugs.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
Nottingham University Hospitals NHS Trust (UK)

When is the study starting and how long is it expected to run for?
January 2010 to January 2018

Who is funding the study?
1. The Stroke Association (UK)
2. The Alzheimer's Society (UK)

Who is the main contact?
Prof. Philip Bath
Philip.Bath@nottingham.ac.uk

Trial website

http://www.podcast-trial.org

Contact information

Type

Scientific

Primary contact

Prof Philip Bath

ORCID ID

Contact details

Division of Stroke Medicine
Institute of Neuroscience
Clinical Sciences Building
City Hospital Campus
Hucknall Road
Nottingham
NG5 1PB
United Kingdom
+44 (0)115 8231765
Philip.Bath@nottingham.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

Version 1.0

Study information

Scientific title

Prevention Of Decline in Cognition After Stroke Trial (PODCAST): a factorial randomised controlled trial of intensive versus guideline (moderate) lowering of blood pressure and lipids

Acronym

PODCAST

Study hypothesis

To study if intensive blood pressure and/or lipid lowering post stroke, is better than moderate blood pressure and/or lipid lowering, to prevent cognitive decline after stroke.

Ethics approval

Nottingham Research Ethics Committee 1, 24/07/2009

Study design

Multicentre prospective randomised open-label blinded end-point controlled partial-factorial phase IV trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Cognitive impairment after stroke

Intervention

The trial will assess whether intensive blood pressure lowering (systolic blood pressure less than 125 mmHg) and lipid lowering (low density lipoprotein [LDL]-cholesterol less than 2.0 mmol/L) is better than moderate blood pressure lowering (systolic blood pressure less than 140 mmHg) and cholesterol lowering (LDL-cholesterol less than 3.0 mmol/L).

Participants with ischaemic stroke will be randomised to both the blood pressure and lipid lowering arms; participants with haemorrhagic stroke will be randomised only to the blood pressure lowering arm.

The study will test management strategies and not individual drugs. Algorithms taking account of 'National Institute of Clinical Excellence, UK Guidelines', relating to stroke, hypertension, lipids and Type 2 Diabetes will aid investigators in treatment decision-making using standard antihypertensive and lipid lowering drugs so that participants are treated as randomised.

The total duration of the trial is 8 years and follow up for participants will range from 1 - 8 years depending on the time of enrolment. The trial intervention will be for the same duration.

Intervention type

Other

Phase

Phase IV

Drug names

Primary outcome measures

Comparison of cognition (Addenbrooke's Cognitive Examination extended to include death) between 'intensive' and 'moderate' BP/lipid lowering groups, measured at baseline, 6, 18, 30, 42, 54, 66, 78, 90 and 96 months.

Secondary outcome measures

For each of BP-lowering and lipid-lowering arms, comparison between 'intensive' and 'moderate' groups:
1. Dementia: measured at 6, 18, 30, 42, 54, 66, 78, 90 and 96 months -
1.1. Using alzheimers disease (AD) - National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and vascular dementia (VaD) - National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherché et l'Enseignement en Neurosciences (NINDS-AIREN)
1.2. With/without recurrent stroke
2. Cognition: all tests at 6, 18, 30, 42, 54, 66, 78, 90 and 96 months, except telephone-administered mini-mental state examination (tMMSE) and Telephone Interview for Cognitive Status (TICS-M) done at 0, 12, 24, 36, 48, 70 and 84 months over the telephone
2.1. Global - mini-mental state examination (MMSE), tMMSE, TICS
2.2. Association - trail making A/B
2.3. STROOP test
2.4. Cognitive decline with/without recurrent stroke
2.5. Ordinal cognition (MMSE greater than 28/23 - 28/10 - 22/less than 10/dementia/dead)
2.6. Informant (IQCODE)
3. Quality of life - EuroQoL, informant (DEMQoL), measured at baseline, 6, 18, 30, 42, 54, 66, 78, 90 and 96 months
4. Depression (Zung), measured at baseline, 6, 18, 30, 42, 54, 66, 78, 90 and 96 months
5. Dependency (modified Rankin Scale [mRS]), measured at baseline, 6, 18, 30, 42, 54, 66, 78, 90 and 96 months
6. Disability (Barthel Index [BI]), measured at baseline, 6, 18, 30, 42, 54, 66, 78, 90 and 96 months
7. Stroke recurrence, measured at baseline and every six months until the end of the trial
8. Myocardial infarction, measured every six months until the end of the trial
9. Composite vascular events (non-fatal stroke, non-fatal MI, fatal vascular), measured every six months until the end of the trial
10. Stroke: fatal/severe non-fatal/mild/transient ischaemic attack [TIA]/none, measured at baseline and every six months until the end of the trial
11. Myocardial infarction: fatal/non-fatal/angina/none, measured at baseline and every six months until the end of the trial
12. Vascular: fatal/non-fatal/none, measured at baseline and every six months until the end of the trial
13. New diabetes, measured at baseline, 6, 18, 30, 42, 54, 66, 78, 90 and 96 months
14. New atrial fibrillation, measured at baseline, 6, 18, 30, 42, 54, 66, 78, 90 and 96 months
15. Residence (home, institution), care package, informal family support, measured at baseline, 6, 18, 30, 42, 54, 66, 78, 90 and 96 months
16. Blood pressure (systolic BP, diastolic BP, pulse pressure, rate-pressure product), measured at baseline, 6, 18, 30, 42, 54, 66, 78, 90 and 96 months
17. Lipids (total cholesterol [TC], triglycerides [TG], HDL, calculated LDL), measured at baseline, 6, 18, 30, 42, 54, 66, 78, 90 and 96 months
18. Neuroimaging (in a subset of participants), measured at baseline and at 3 years

Overall trial start date

01/01/2010

Overall trial end date

01/01/2018

Reason abandoned

Eligibility

Participant inclusion criteria

1. Age greater than 70 years and telephone-administered mini-mental state examination (MMSE) greater than 16; or aged greater than 60 years and telephone-MMSE 17 - 19, either sex
2. Functionally independent (modified Rankin Scale [mRS] 0 - 2)
3. Ischaemic stroke (any cortical Oxfordshire Community Stroke Project [OCSP]/Trial of ORG 10172 in Acute Stroke Treatment [TOAST] type) or primary intracerebral haemorrhage (cortical or basal ganglia)
4. Three to seven months post-event (to allow cognitive, neurological, blood pressure [BP] and lipid stabilisation, but avoid attrition)
5. Systolic BP 125 - 170 mmHg
6. Total cholesterol 3 - 8 mmol/l
7. Presence of a reporter: partner, sibling, child, friend (for Informant Questionnaire of Cognitive Decline [IQCODE]/Dementia Quality of Life [DEMQoL])
8. Capacity and willingness to give consent

Participant type

Patient

Age group

Senior

Gender

Both

Target number of participants

3400 participants (600 in the start-up phase and 2800 in the main phase)

Participant exclusion criteria

1. Participants not meeting inclusion criteria
2. Subarachnoid haemorrhage
3. Secondary intracranial haemorrhage (trauma, arteriovenous malformation [AVM], cavernoma)
4. Posterior circulation ischaemic stroke
5. Posterior circulation haemorrhage
6. No computed tomography (CT)/magnetic resonance imaging (MRI) during index stroke
7. Inability to give consent or do study measures, e.g. severe dysphasia, weakness of dominant arm
8. Severe hypertension (systolic BP greater than 170 mmHg)
9. Definite need for 'intensive' BP control
10. Severe hypercholesterolemia (total cholesterol [TC] greater than 8 mmol/l)
11. Definite need for 'high intensity' statin or ezetimibe
12. Definite need for a cholinesterase inhibitor
13. Familial stroke associated with dementia, e.g. cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL)
14. Chronic renal failure: glomerular filtration rate (GFR) less than 50
15. Liver disease, alanine aminotransferase (ALT) greater than 60
16. Ongoing participation in trials involving drug and/or devices, or within the last 3 months

Recruitment start date

01/01/2010

Recruitment end date

01/01/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Institute of Neuroscience
Notttingham
NG5 1PB
United Kingdom

Sponsor information

Organisation

The University of Nottingham (UK)

Sponsor details

c/o Mr Paul Cartledge
Head of Research Grants and Contracts
Research Innovation Services
King's Meadow Campus
Lenton Lane
Nottingham
NG7 2NR
United Kingdom
+44 (0)115 951 5679
paul.cartledge@nottingham.ac.uk

Sponsor type

University/education

Website

http://www.nottingham.ac.uk

Funders

Funder type

Charity

Funder name

Stroke Association (UK) (ref: TSA2008/09)

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

professional associations and societies

Location

United Kingdom

Funder name

Alzheimer's Society (UK) (ref: TSA 2008/09)

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

professional associations and societies

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2015 results in http://www.ncbi.nlm.nih.gov/pubmed/26545986
2013 protocol in http://www.ncbi.nlm.nih.gov/pubmed/24266960

Publication citations

  1. Protocol

    Blackburn DJ, Krishnan K, Fox L, Ballard C, Burns A, Ford GA, Mant J, Passmore P, Pocock S, Reckless J, Sprigg N, Stewart R, Wardlaw J, Bath PM, Prevention of Decline in Cognition after Stroke Trial (PODCAST): a study protocol for a factorial randomised controlled trial of intensive versus guideline lowering of blood pressure and lipids., Trials, 2013, 14, 401, doi: 10.1186/1745-6215-14-401.

Additional files

Editorial Notes

04/03/2016: Plain English summary added. 09/11/2015: Publication reference added.